Pyridoxal Phosphate Inhibits Pituitary Cell Proliferation and Hormone Secretion

Abstract

Pyridoxal phosphate (PLP), a bioactive form of pyridoxine, dose-dependently (10-1000 microm) inhibited cell proliferation in rat pituitary MMQ and GH3 cells and in mouse AtT-20 cells. After 4 d, MMQ cell numbers were reduced by up to 81%, GH3 cell numbers were reduced by up to 64% (P < 0.05), and AtT-20 cell numbers were reduced by up to 90%. Cell proliferation rates recovered and dose-dependently reverted to control levels after PLP withdrawal. After 4 d, PLP (400 and 1000 microm) decreased [3H]thymidine incorporation by up to 71% (P < 0.05). PLP (400-1000 microm) reduced GH3 cell GH and prolactin secretion and AtT-20 cell ACTH secretion (adjusted for cell number) by approximately 70% after 2 d. The 100 microm PLP also inhibited prolactin secretion (65%, P < 0.05) in primary rat pituitary cells treated for 2 d. PLP decreased the percentage of AtT-20 and GH3 cells in S phase and increased those in G0-G1 phase. Furthermore, PLP induced AtT-20 and GH3 cell apoptosis (28 vs. 6, P < 0.05; 26 vs. 3, P < 0.05, respectively) and dose-dependently reduced content of the antiapoptosis gene Bcl-2. These results indicate that pharmacological doses of PLP inhibit pituitary cell proliferation and hormone secretion, in part mediated through PLP-induced cell-cycle arrest and apoptosis. Pyridoxine may therefore be appropriate for testing as a relatively safe drug for adjuvant treatment of hormone-secreting pituitary adenomas.

Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer

“…Our data suggest that inhibition of LMWPTP through Vitamin B6 may provide one possible explanation for these findings. Indeed, in pituitary cells PLP has been shown to induce cell cycle arrest [ 24 ], which corresponds well with the cell cycle block and apoptosis observed in our study, and suggests that LMWPTP inhibition may be a valuable avenue for treatment of CRC. Earlier reports have suggested that LMWPTP could modulate chemoresistance of cancer cells [ 25 ].…”

Environmental Factors Affecting Thyroid-Stimulating Hormone and Thyroid Hormone Levels

“…Other vitamins . A deficiency of other vitamins such as vitamin A [ 185 , 186 ], vitamin B 12 [ 187 ], vitamin B 6 [ 188 , 189 ] and vitamin E [ 190 ] has also been observed in thyroid diseases. Supplementation with vitamin C and E [ 191 , 192 ], vitamin A [ 193 ], vitamin B 12 [ 194 ] and vitamin B 6 (reviewed in [ 195 ]) has been suggested to improve thyroid health.…”

Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome

“…As a result, D-glutamic acid up-regulation in PCOS may indicate a decrease in oocyte utilization and subsequent accumulation in the FF, affecting its growth. Phenylalanine metabolism is crucial for the growth and development of the oocyte and has been linked to ovulatory dysfunction in women [ 118 , 122 , 213 , 214 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 ]. Elevated levels of salicylic acid are involved in phenylalanine metabolism [ 122 ].…”